Essential Hypertension and Its Causes

Neural and Non-Neural Mechanisms

Paul I. Korner

With an extremely broad reach, this book aims to give a balanced view of the causes of EH, its neural, genetic, and environmental causes

Gives a detailed analysis of the main components of the circulatory control system

Suggests that physiological systems analysis in a complex disorder like EH is a valuable tool for using the advances in molecular biology to best advantage.

Essential Hypertension and Its Causes

Neural and Non-Neural Mechanisms

Paul I. Korner

Description

This new account of the pathogenesis of essential hypertension (EH) represents a detailed analysis of the main components of the circulatory control system. The latter's properties resemble those of man-made adaptive control systems in which regulatory parameters are altered when operating conditions exceed certain limits, often through neural mechanisms.

Inheritance of EH depends on both genes and environment. The high blood pressure (BP) genes have not yet been definitively identified, whilst the main environmental causes are mental stress, high dietary salt intake and obesity. EH occurs as two major syndromes, each initiated by chronic stress: 1) Stress-and-salt related EH, and 2) Hypertensive obesity. Stress is perceived by the cortex, from which
increased dopaminergic (DA) neuron activity stimulates the hypothalamic defense area, raising sympathetic neural activity (SNA) and BP. Normally these subside quickly when the stress is over, but in those susceptible to EH the DA synapses become sensitized so that the defense response is evoked by ever lower levels of stress. Sensitization is common in memory circuits, but not in autonomic neurons, so that this property in EH may be genetically determined.

Stress-related hypertension increases hypothalamic responsiveness to high salt, resulting in further rises in SNA and BP. Later, non-neural functional changes (e.g. reduction in nitric oxide) and the structural remodeling of resistance vessels further enhance the vasoconstriction. In contrast, in those developing
hypertensive obesity food consumption is excessive, which transiently alleviates stress-related anxiety. The brain ignores the leptin-mediated signals that normally curb appetite, contrasting with normal energy regulation in SSR-EH. In hypertensive obesity, the SNA pattern is similar to that in SSR-EH, but vasoconstriction is masked by vasodilatation and fluid retention due to hyperinsulinemia. This syndrome is a volume overload hypertension, where high cardiac output, renal impairment and other non-neural factors contribute to the elevation of BP.

Other topics include the role of various transmitters in autonomic regulation; the place of baroreflexes in the intact organism; why exercise training lowers resting BP; obstructive sleep apnea; non-pharmacological and drug
treatment of EH; the role of the kidney in EH and in different types of renal hypertension and the pathogenesis of the Japanese spontaneously hypertensive rat, which provides a valuable animal model for EH.

The work suggests that physiological systems analysis in a complex disorder like EH is a valuable tool for using the great advances in molecular biology to best advantage.

Essential Hypertension and Its Causes

Neural and Non-Neural Mechanisms

Paul I. Korner

Table of Contents

Preface. Table of Contents. Acknowledgements. I. Introduction. 1. A Short History and some Clinical AspectsII. Biological Control. 2. The Nature of the Cardiovascular Control System3. Blood Pressure GeneticsIII. Output Analysis: Pointers to Neural Involvement. 4. Determinants of Long-Term Elevation of Arterial Pressure5. Output Patterns in Non-Obese HypertensivesIV. Intrinsic Cardiovascular Properties in Hypertension. 6. The Peripheral Vascular Integrator7. Cardiac PerformanceV. Cellular and Integrative Aspects of Circulatory Control. 8. CNS Cardiovascular Pathways: Role of Fast and Slow Transmitters9. "Whole Organism" Baroreflexes10. Exercise Training and its Long-Term
Effects on Blood Pressure: Linkage to Somatic MovementVI. The Brain as the Source of Lifestyle-Related Hypertension. 11. Psychosocial Stress and Hypertension12. Salt, Other Dietary Factors, and Blood Pressure13. Normotensive and Hypertensive Obesity14. Obstructive Sleep ApnoeaVII. Neural Involvement in other Types of Hypertension. 15. More About the Kidney in Hypertension16. SHR Hypertension and its CausesVIII. Synthesis. 17. Pathogenesis of Essential Hypertension: Implications for Prevention and TreatmentIndex.

Essential Hypertension and Its Causes

Neural and Non-Neural Mechanisms

Paul I. Korner

Author Information

Paul Korner is Emeritus Professor of Medicine, Monash University, and Emeritus Director of the Baker Medical Research Institute. He was Foundation Professor of Physiology, University of New South Wales (1960-68); Scandrett Professor of Cardiology, University of Sydney (1968-1974); Director of the Baker Medical Research Institute and Professor of Medicine, Monash University (1975-1990).

Essential Hypertension and Its Causes

Neural and Non-Neural Mechanisms

Paul I. Korner

Reviews and Awards

"Dr. Korner successfully integrates vast amounts of information learned from research on the pathogenesis of essential hypertension into one comprehensive reference. Initial alterations of neural pressure regulatory system are expertly detailed providing targeted areas for expanded research."--Doody's

"...an invaluable resource to physicians and researchers in hypertension."--British Journal of Hospital Medicine

"Overall Essential Hypertension and Its Causes offers a fresh perspective on the putative causes of hypertension. This perspective may shift the focus of some research to the further illumination of neural mechanisms in the hope of finding new therapeutic measures - or perhaps a way to prevent essential hypertension altogether."--New England Journal of Medicine

"...We have long been missing the publication of books giving a strong,personal, even if controversial, general view of hypertension, such as those once authored by Volhard, Pickering and Page. Now, Paul Korner has provided one."--Journal of Hypertension

"This is a rare treat. After a lifetime of research and scholarship one of our best scientists plants a stake in the ground and.. gets into a serious and erudite analysis of the world's greatest preventable health problem. Essential Hypertension and Its Causes offers a synthesis which can never be gained from a standard text book. It will appeal to all those with a serious interest in hypertension."--Heart, Lung, and Circulation